Strong evidence suggests glutamate or aspartate as the transmitter employed at certain excitatory synapses in the rat hippocampal formation. These synapses have been selected as models for analysis of glutamate/aspartate mechanisms. Two sodium-independent binding sites for glutamate have been identified and characterized in preparations of hippocampal synaptic membranes. The role of these binding sites as synaptic receptors will be evaluated by pharmacological and physiological comparisons with synaptic responses in the hippocampal slice preparation and with the ability of excitatory amino acids and their antagonists to modulate the opening of sodium channels in these slices. The muscle relaxant, baclofen, which has been proposed to act selectively at excitatory amino acid-utilizing synapses, will be tested for its effects on transmission at hippocampal synapses. The relation between the neuroexcitatory, epileptogenic and neurotoxic activities of acidic amino acids will be further explored in the hippocampal model with use of electrographic and membraane binding techniques. Finally, the effects of baclofen and autoreceptors on the release of glutamate and aspartate will be examined. These studies will aid our understanding of excitatory transmission in the central nervous system. Their ultimate goal is to provide basic information needed to develop pharmacotherapies aimed at excitatory amino acid systems.